Human Experimentation in Public Schools: How Schools Served as Sites of Vaccine Trials in the 20th Century.

Schools have long been critical partners for public health authorities in achieving widespread vaccination. In the mid-20th century, however, public schools also served as sites of large-scale experiments on novel vaccines. Through examining the experimental diphtheria, polio, and measles vaccine trials, I explored the implications of using schools in this manner, as well as the continuities and discontinuities among the three cases. Common to all of them was that the use of schools brought decision-making into the public sphere, subjecting parents to social pressures and the influences of school officials and community members. However, the effects of using schools varied as well, as their social and institutional significance interacted differently with the narratives surrounding each disease, the public's changing perception of medicine and science, and society's changing values. These insights show not only the power of public institutions to influence opinions and perceptions, but also the subtle forces that one's authority figures, peers, and community members may bring to a seemingly private decision-making process. These considerations are relevant to health interventions today, such as the complex debate over community consent in global health research. (Am J Public Health. 2018;108:1015-1022. doi: 10.2105/AJPH.2018.304423).

[Diphtheria in the military forces: lessons and current status of prophylaxis, prospects of epidemiological control process].

We analyzed the epidemiological situation of diphtheria in the world and in Russia and experience of mass vaccination of military personnel and civil population with diphtheria toxoid for the last 50 years. Early diagnosis of diphtheria in military personnel has a prognostic value. Authors described the peculiarities of epidemiological process of diphtheria in military personnel in 80-90 years of 20th century and organizational aspects of mass vaccination with diphtheria toxoid. Authors analyzed current problems of epidemiology and prophylaxis of diphtheria in military personnel and civil population and possible developments. According to long-term prognosis authors mentioned the increase of morbidity and came to conclusion that it is necessary enhance the epidemiological surveillance. Authors presented prospect ways of improvement of vaccination and rational approaches to immunization of military personnel under positive long-term epidemiological situation.

The diphtheria vaccine debacle of 1940 that ushered in comprehensive childhood immunization in the United Kingdom.

In January 1940 British Ministry of Health circular 1307 proposed the introduction of mass childhood diphtheria immunization. This was a policy reversal after a decade during which opportunities for diphtheria prophylaxis were ignored, or resisted on grounds of cost. Diphtheria toxoid was to be the first of many centrally funded childhood immunizations in the UK and it set a pattern that has now held good for over 70 years. The circumstances in 1940 were particularly fortuitous, and diphtheria toxoid has since given successive generations of children a lifetime's protection from the disease; but difficulties have been experienced in introducing and evaluating some of the more recent immunizations, and in maintaining and justifying them in the face of parental scepticism and academic or pressure-group opposition, however ill-founded this may have been. The task of decision-making with regard to new candidate vaccines demands a careful balancing against the costs of the expected benefits during the recipient's lifespan.

Emil von Behring and serum therapy.

Emil von Behring is the father of serum therapy. We present an overview of the development of this important tool in the treatment of diphtheria. In a historical context Behring's work reflects the scientific spirit of fin de siècle Berlin.

Immunization and the American way: 4 childhood vaccines.

Childhood immunization constitutes one of the great success stories of American public health in the 20th century. This essay provides a historical examination of this topic through 4 particularly important examples: diphtheria, pertussis, polio, and measles. Each case study illustrates how new vaccines have posed unique challenges related to basic science, clinical trial methodology, medical ethics, and public acceptance. A brief comparison of each story to the experience of Great Britain, however, suggests an underlying unity connecting all 4 examples. Whereas the British led the way in introducing formal clinical trial methodology in the field of immunization development, the Americans excelled in the rapid translation of laboratory knowledge into strategies suitable for mass application. Although this distinction appears to have diminished in recent years, it offers insight into the sources of creativity underlying American vaccine development and the corresponding difficulties sometimes created for utilizing vaccines fruits rationally.

A short history of the use of animals in vaccine development and quality control.

Man has been using animals since early times to gain an insight into health, illness and death. The oldest known medical standard work, the Corpus Hippocraticum (circa 350 BC), contains descriptions of experiments on pigs. Although the first attempt at immunoprophylaxis dates as far back as the 6th century (variolation was practised in China to protect people against smallpox), it was not until the middle of the 19th century that animal experimentation acquired full scientific status in the development and quality control of immunobiological products. It was Louis Pasteur and Robert Koch who, through studies on animals, succeeded in underpinning the causal relationship between infectious diseases and micro-organisms, thus opening the way to the discovery of effective therapeutic and prophylactic agents for a number of these diseases. In several respects, the experimental animal work carried out in the last decade of the 19th century to find an effective and reliable way of treating and preventing diphtheria determined the use of animals. Many common routine animal tests in the quality control of immunobiologicals arose from diphtheria research. Conversely, diphtheria was one of the first diseases where experimental animal research laid the foundation for effectively reducing child mortality. This had a very profound impact on the attitude of society towards animal experiments in those days and almost completely eliminated the growing influence of the antivivisection movement. The interest in the possibilities of replacement, reduction and refinement (the Three-Rs concept) of the use of laboratory animals is increasing for several reasons, including concern about animal welfare. The root of animal welfare can be traced back to the 18th century with the formulation of utilitarian ethics. One characteristic feature of these ethics was that the interests of any creature which is submitted to any procedure should be taken into consideration. This presentation sets out some major historical contributions of animal experiments to the development and quality control of immunobiologicals. Attention is also paid to the changing attitude of society towards animal experiments and its impact on the development of alternative methods. It is concluded that, although animal experiments have played an important part, a new area is now beginning in which increasing emphasis will be placed on in vitro methods.

Rho(D) immunoglobulin (RhoGAM): how it came into being.

The story of Rho(D) immunoglobulin (RhoGAM) begins in 1909 with Theobald Smith, Fabyan Professor of Comparative Pathology at Harvard, and ends in the 1960s with completion of the clinical trials. Important in the development of RhoGAM were the search for a safe diphtheria vaccine, an interest in butterfly mimicry, the discovery of the Rhesus factor, and the contribution of Sing Sing prison inmates--seemingly unrelated occurrences. But, when all were combined, the riddle of erythroblastosis fetalis was solved.

[Physician, state and public health: the campaign against diphtheria in Belgium (1894-1914)]. / Arts, staat en volksgezondheid: de strijd tegen de difterie in belgië (1894-1914).

On 100 deaths caused by diphtheria in Belgium at the end to the 19th century, 90% had not reached the age of 6. In the beginning of the nineties an antitoxin had been developed against the so called "terror of mothers". Very slowly, the production of sera took place, first of all in Germany, after 1894 in our country too. The battle against diphtheria became the subject of parliamentary debates (in the years 1894-1895 and 1900) and of several comments and articles in the Belgian medical press. The authorities followed the evolution of morbidity closely, commissions were charged with the study of the effectiveness of sera and of the foundation, if necessary, of an institution for serotherapy. As a result of an intensive campaign of serotherapy, the decrease of mortality rates due to diphtheria was sensational after 1910.